scholarly journals Macrophage control of normal and leukemic erythropoiesis: identification of the macrophage-derived erythroid suppressing activity as interleukin-1 and the mediator of its in vivo action as tumor necrosis factor

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2328-2334 ◽  
Author(s):  
P Furmanski ◽  
CS Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Friend Virus ◽  
Erythroid Progenitors ◽  
Simultaneous Treatment ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor

Abstract Macrophages have been shown to directly influence the growth and development of mature erythroid progenitors (CFU-E) in normal and erythroleukemic mice. We examined the mechanism by which macrophages mediate their effect on in vivo erythropoiesis. As reported for whole macrophages, serum-free supernatants (SN) from normal resident peritoneal macrophages suppressed in vivo normal and conventional Friend virus (CFV)-infected CFU-E and caused clinical regression of CFV- induced leukemia in mice. Macrophage SN had no effect on the erythropoietin (EPO)-independent CFU-E characteristic of infection with the polycythemia-inducing strain of Friend virus (FVP), or progression of FVP leukemia. Using biochemical, immunologic, and functional assays, the erythrosuppressive factor in macrophage SN was identified as interleukin-1 alpha (IL-1 alpha). The in vivo erythroid suppressive effects of macrophages, macrophage SN, and IL-1 alpha were reversed by simultaneous treatment with EPO. IL-1 alpha itself had no effect on CFU- E colony formation in vitro. Pretreatment of animals with antibodies to murine tumor necrosis factor-alpha (TNF-alpha) completely abrogated the suppression of CFU-E by macrophages, macrophage SN, or human recombinant IL-1 alpha. These results suggest that macrophages regulate erythropoiesis by production of IL-1 alpha, which in turn mediates its in vivo suppressive effects on CFU-E through TNF.

scholarly journals Macrophage control of normal and leukemic erythropoiesis: identification of the macrophage-derived erythroid suppressing activity as interleukin-1 and the mediator of its in vivo action as tumor necrosis factor

Blood ◽  
1990 ◽  
Vol 75 (12) ◽  
pp. 2328-2334
Author(s):  
P Furmanski ◽  
CS Johnson
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Friend Virus ◽  
Erythroid Progenitors ◽  
Simultaneous Treatment ◽  
Necrosis Factor Alpha ◽  
Necrosis Factor

Macrophages have been shown to directly influence the growth and development of mature erythroid progenitors (CFU-E) in normal and erythroleukemic mice. We examined the mechanism by which macrophages mediate their effect on in vivo erythropoiesis. As reported for whole macrophages, serum-free supernatants (SN) from normal resident peritoneal macrophages suppressed in vivo normal and conventional Friend virus (CFV)-infected CFU-E and caused clinical regression of CFV- induced leukemia in mice. Macrophage SN had no effect on the erythropoietin (EPO)-independent CFU-E characteristic of infection with the polycythemia-inducing strain of Friend virus (FVP), or progression of FVP leukemia. Using biochemical, immunologic, and functional assays, the erythrosuppressive factor in macrophage SN was identified as interleukin-1 alpha (IL-1 alpha). The in vivo erythroid suppressive effects of macrophages, macrophage SN, and IL-1 alpha were reversed by simultaneous treatment with EPO. IL-1 alpha itself had no effect on CFU- E colony formation in vitro. Pretreatment of animals with antibodies to murine tumor necrosis factor-alpha (TNF-alpha) completely abrogated the suppression of CFU-E by macrophages, macrophage SN, or human recombinant IL-1 alpha. These results suggest that macrophages regulate erythropoiesis by production of IL-1 alpha, which in turn mediates its in vivo suppressive effects on CFU-E through TNF.

scholarly journals Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

1991 ◽  
Vol 173 (3) ◽  
pp. 699-703 ◽  
Author(s):  
E P Sampaio ◽  
E N Sarno ◽  
R Galilly ◽  
Z A Cohn ◽  
G Kaplan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

scholarly journals Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine meniscus in vitro

2007 ◽  
Vol 15 (9) ◽  
pp. 1053-1060 ◽  
Author(s):  
A. Hennerbichler ◽  
F.T. Moutos ◽  
D. Hennerbichler ◽  
J.B. Weinberg ◽  
F. Guilak
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Activation of PPARγ Inhibits TLR4 Signal Transduction Pathway in Melanoma Cancer In Vitro

2020 ◽  
Vol 10 (3) ◽  
pp. 458-463
Author(s):  
Nasim Dana ◽  
Golnaz Vaseghi ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Melanoma Cancer ◽  
Anticancer Effects ◽  
Factor Alpha ◽  
Tlr4 Signaling Pathway ◽  
Necrosis Factor

Purpose : Although peroxisome proliferator-activated receptor γ (PPARγ) is known as a regulator of fatty acid storage, fat cell differentiation, glucose and lipid metabolism, recent studies show that PPARγ has anticancer effects. The mechanisms of PPARγ activation in melanoma cancer remain unclarified. Recently, increased TLR4 expression has been associated with the melanoma cancer progression. We investigated whether the anti-cancer effect of PPARγ is through regulating TLR4 signaling pathway. Methods: Mouse melanoma cells (B16F10) were treated in different groups: control, pioglitazone (1, 10, 100, 300 µmol/L), lipopolysaccharide (LPS) (5 µg/mL) and LPS + pioglitazone. In another experiment, they were treated with CLI-095 (1 μM), and after 1 hour pioglitazone was added and subsequently stimulated with LPS. MTT assay was performed to measure the cell viability in vitro. The expression of Tlr4, Myd88, Nf-κb genes were evaluated by quantitative reverse transcription PCR (qRT-PCR) in different groups. The concentration of tumor necrosis factor alpha and Interleukin 1 beta in the cell culture medium were measured by enzyme-linked immunosorbent assay (ELISA) kits. Results: We show that activation of PPARγ by its agonist, pioglitazone, reduces cell proliferation, Tlr-4, Myd-88, Nf-kb mRNA expression, and tumor necrosis factor-alpha (TNF-α) production but not interleukin-1 β (IL-1β) in B16F10 LPS–stimulated cells in vitro. Moreover, treatment of B16F10 cells with TLR4 inhibitor prior treatment with pioglitazone indicate that the anticancer effects of pioglitazone on melanoma cells was dependent on TLR4. Conclusion: The results indicate that pioglitazone has a beneficial protective effect against melanoma by affecting the TLR4 signaling pathway.

scholarly journals Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1216-1225 ◽  
Author(s):  
F Rosselli ◽  
J Sanceau ◽  
E Gluckman ◽  
J Wietzerbin ◽  
E Moustacchi
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Fanconi Anemia ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract We have previously shown an unbalanced cytokine production in Fanconi anemia (FA) cells, ie, an underproduction of interleukin 6 (IL-6) during growth. Among a number of cytokines analyzed, the only other anomalies detected concern tumor necrosis factor alpha (TNF alpha). In comparison to normal cells, this cytokine is overproduced by FA lymphoblasts from the four genetic complementation groups. Indeed, up to an eight-fold increase in TNF alpha is observed in the growth medium of FA cells. Moreover, addition of anti-TNF alpha antibodies partially corrects the FA hypersensitivity to treatment by mitomycin C (MMC). Treatment of FA cells with IL-6, which partially restored an almost normal sensitivity to MMC of FA cells also reduces the TNF alpha overproduction in FA lymphoblasts. No anomalies at the molecular level (Southern and Northern blot analyses) are detected for the TNF alpha gene and its mRNA. We have investigated the in vivo situation by assaying TNF alpha levels in the serum from FA homozygotes and obligate heterozygotes. In contrast to normal healthy donors or to aplastic anemia patients in whom serum TNF alpha is present only in trace amounts, all 36 FA patients and 21 FA parents monitored show a significantly (P < .001) higher level of serum TNF alpha activity. Consequently, abnormal TNF alpha production seems to be associated with the FA genetic background.

Constitutive production of tumor necrosis factor-alpha in hairy cell leukemia: possible role in the pathogenesis of the cytopenia(s) and effect of treatment with interferon-alpha.

1992 ◽  
Vol 10 (6) ◽  
pp. 954-959 ◽  
Author(s):  
R Foa ◽  
A Guarini ◽  
P Francia di Celle ◽  
L Trentin ◽  
A Gillio Tos ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Erythroid Progenitors ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Circulating Levels ◽  
Necrosis Factor

PURPOSE In view of the pleomorphic role cytokines play in human lymphoproliferative disorders, we investigated the possible involvement of tumor necrosis factor-alpha (TNF) in hairy cell leukemia (HCL). PATIENTS AND METHODS The levels of TNF were measured in the serum of untreated patients, and in the culture supernatants of unstimulated and stimulated enriched hairy cells (HC). Furthermore, the presence of TNF mRNA transcripts in HC was analyzed. The possibility that HC could inhibit the in vitro growth of normal erythroid progenitors via the release of TNF was also investigated. Finally, in an attempt to correlate the circulating levels of TNF with the course of the disease, these were retested during and after treatment with interferon-alpha (IFN). RESULTS Significantly increased levels of TNF were found in the sera of untreated HCL patients compared with normal control sera were seen from patients with other diseases (P less than .001), with values greater than 10 pg/mL in 21 of 42 samples tested. A significant decrease (P less than .01) of TNF levels was recorded following IFN-2a administration in 16 cases with detectable pretreatment serum levels of TNF. In two cases, an increase in TNF values was associated with persistence or progression of disease. The likelihood that the circulating levels of TNF were caused by the pathologic cells is supported by the evidence that purified HC may release TNF spontaneously. The values can be markedly increased following in vitro activation with the phorbol ester 12-0-tetradecanoylphorbol-13 acetate (PMA), with B-cell growth factor (BCGF), and, to a further extent, with the combination of PMA and BCGF. Furthermore, the constitutive mRNA for TNF was found in seven of eight HC samples analyzed. Although supernatants of enriched HC, were capable of reducing the growth of normal bone marrow erythroid progenitors by 50%, duplicate experiments using an anti-TNF antibody produced an almost complete disappearance of the inhibitory effect. CONCLUSION The results of this study suggest that TNF plays an important role in the pathogenesis of the cytopenia(s) characteristically associated with HCL.

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